The H3K9 methylation writer SETDB1 and its reader MPP8 cooperate to silence satellite DNA repeats in mouse embryonic stem cells

Paola Cruz-Tapias, Philippe Robin, Julien Pontis, Laurence Del Maestro, Slimane Ait-Si-Ali

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

SETDB1 (SET Domain Bifurcated histone lysine methyltransferase 1) is a key lysine methyltransferase (KMT) required in embryonic stem cells (ESCs), where it silences transposable elements and DNA repeats via histone H3 lysine 9 tri-methylation (H3K9me3), independently of DNA methylation. The H3K9 methylation reader M-Phase Phosphoprotein 8 (MPP8) is highly expressed in ESCs and germline cells. Although evidence of a cooperation between H3K9 KMTs and MPP8 in committed cells has emerged, the interplay between H3K9 methylation writers and MPP8 in ESCs remains elusive. Here, we show that MPP8 interacts physically and functionally with SETDB1 in ESCs. Indeed, combining biochemical, transcriptomic and genomic analyses, we found that MPP8 and SETDB1 co-regulate a significant number of common genomic targets, especially the DNA satellite repeats. Together, our data point to a model in which the silencing of a class of repeated sequences in ESCs involves the cooperation between the H3K9 methylation writer SETDB1 and its reader MPP8.

Original languageEnglish (US)
Article number750
JournalGenes
Volume10
Issue number10
DOIs
StatePublished - Oct 2019

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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